沉默微小RNA-34a对类风湿关节炎大鼠症状改善和血清炎症因子水平的影响及其机制  

Effect of silencing microRNA-34a on symptom remission and serum levels ofinflammatory factors in rats with rheumatoid arthritis and its mechanism

作　　者：李刚[1] 刘亚东[2] 徐昕[1] 张鹏[3] 熊敏[4] 田大为[3] LI Gang;LIU Ya-dong;XU Xin;ZHANG Peng;XIONG Min;TIAN Da-wei(Department of Sports Medicine,Sinopharm Group Dongfeng General Hospital Affiliated to Hubei University of Medicine,Shiyan 442008,China;Department of Hand-Foot-Ankle Microsurgery,Sinopharm Group Dongfeng General Hospital Affiliated to Hubei University of Medicine,Shiyan 442008,China;Department of Bone and Joint Surgery,Sinopharm Group Dongfeng General Hospital Affiliated to Hubei University of Medicine,Shiyan 442008,China;Department of Spine Surgery,Sinopharm Group Dongfeng General Hospital Affiliated to Hubei University of Medicine,Shiyan 442008,China)

机构地区：[1]湖北医药学院附属国药东风总医院运动医学科,十堰市442008 [2]湖北医药学院附属国药东风总医院手外足踝显微外科,十堰市442008 [3]湖北医药学院附属国药东风总医院骨关节外,十堰市442008 [4]湖北医药学院附属国药东风总医院脊柱外科,十堰市442008

出　　处：《广西医学》2021年第13期1598-1603,共6页Guangxi Medical Journal

基　　金：湖北省卫计委科研项目(WJ2015MB217)。

摘　　要：目的探讨沉默微小RNA-34a(miRNA-34a)对类风湿关节炎大鼠关节症状改善和血清炎症因子水平的影响及其机制。方法将60只大鼠随机分为空白组、模型组、过表达组、沉默组各15只,其中模型组、过表达组、沉默组建立类风湿关节炎模型。建模成功后,于沉默组大鼠双后肢骨关节处注射含10μL miRNA-34a抑制载体的慢病毒悬液,过表达组大鼠双后肢骨关节处注射含10μL miRNA-34a过表达载体的慢病毒悬液,空白组、模型组大鼠不做任何处理。评价各组大鼠足跖肿胀度、关节组织评分;并检测各组大鼠血清肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、细胞间黏附因子1(ICAM-1)水平,成骨细胞增殖率和凋亡率,以及关节组织中Toll样受体4(TLR4)、核因子κB抑制蛋白α(IκBα)mRNA表达水平。结果与空白组相比,其他3组大鼠血清TNF-α、IL-1β、ICAM-1水平,足跖肿胀度和关节组织评分,以及关节组织TLR4、IκBαmRNA表达水平均增加(P<0.05);过表达组、模型组、沉默组大鼠血清TNF-α、IL-1β、ICAM-1水平,足跖肿胀度、关节组织评分以及关节组织TLR4、IκBαmRNA表达水平依次降低(均P<0.05)。各时间点,空白组成骨细胞增殖率高于其他3组,凋亡率低于其他3组,过表达组、模型组、沉默组大鼠成骨细胞增殖率依次升高,凋亡率依次降低(均P<0.05)。结论沉默miRNA-34a可抑制类风湿关节炎大鼠的炎症反应并缓解关节症状,其机制可能与其下调TLR4/IκBα信号通路表达,从而促进成骨细胞增殖、抑制成骨细胞凋亡有关。Objective To explore the effect of silencing microRNA-34a(miRNA-34a)on joint symptom remission and serum levels of inflammatory factors in rats with rheumatoid arthritis and its mechanism.Methods Sixty rats were randomly divided into blank group,model group,overexpression group and silencing group,with 15 rats in each group.The model of rheumatoid arthritis was established in the model,overexpression and silencing groups.AfteRsuccessful modeling,rats in the silencing group were injected with lentivirus suspension containing 10μL miRNA-34a inhibition vectoRin the joints of two posterioRlimbs,rats in the overexpression group were injected with lentivirus suspension containing 10μL miRNA-34a overexpression vectoRin the joints of two posterioRlimbs,and rats in the blank and model groups did not receive any treatment.The degree of plantaRswelling and the score of joint tissue were assessed in each group;in addition,the detection was performed on the levels of serum tumoRnecrosis factoRα(TNF-α),interleukin 1β(IL-1β)and intercellulaRadhesion molecule 1(ICAM-1),proliferation rate and apoptosis rate of osteoblasts,as well as mRNA expression levels of Toll-like receptoR4(TLR4),nucleaRfactoRκB inhibitory proteinα(IκBα)in joint tissues.Results Compared with the blank group,rats in the remaining three groups yielded higheRlevels of serum TNF-α,IL-1βand ICAM-1,increased plantaRswelling degree and joint tissue score,as well as elevated expression levels of TLR4 and IκBαmRNAs in joint tissues(P<0.05);serum TNF-α,IL-1βand ICAM-1 levels,plantaRswelling degree,joint tissue score,as well as the expression levels of TLR4 and IκBαmRNAs in joint tissues decreased in the sequence of the overexpression group,the model group and the silencing group(all P<005).At each time point,the blank group exhibited higheRproliferation rate of osteoblasts and loweRapoptosis rate as compared with the remaining three groups,the osteoblast proliferation rate increased and the apoptosis rate decreased in turn in the overexpression group,

关 键 词：类风湿关节炎 微小RNA-34a 成骨细胞 细胞凋亡 细胞增殖 炎症反应 TOLL样受体4 核因子κB抑制蛋白α 大鼠 

分 类 号：R539.22[医药卫生—内科学]